Aim:Serum amyloid A(SAA)is an important mammalian acute reactant.Here,weaim to investigate the effect of SAA on apoptosis and its mechanism of action inhuman amniotic WISH cells.Methods:The expression of formyl peptide receptor(FPRL1),which is reported as a SAA receptor,was tested using RT-PCR andligand binding assay with radio-labeled FPRL1 ligand.The effect of SAA onproliferating cell population was evaluated by thymidine incorporation assay.The protein phosphorylation levels and caspase-3 activity were detected by West-ern blot assay.Results:SAA inhibits thymidine incorporation in human amnioticWISH cells.A SAA-induced decrease of proliferating cell population was accom-panied with nuclear condensation and caspase-3 activation in WISH cells,sug-gesting that SAA induces WISH cell apoptosis.Since FPRL1 has been reportedas a SAA receptor,we investigated the effects of several FRPL1 agonists on aproliferating cell population in WISH cells.Among the tested FPRL1 agonists,only SAA induced a decrease of proliferating cell population in WISH cells.Onthe downstream signaling of SAA,we found that SAA stimulated extracellularsignal-regulated kinase and p38 kinase,which were not inhibited by pertussistoxin(PTX),ruling out the role of PTX-sensitive G-proteins.Furthermore a SAA-induced decrease of proliferating cell population was not affected by PTX,sug-gesting that SAA inhibits WISH cell apoptosis in a PTX-sensitive G-protein-independent manner.A SAA-induced decrease of a proliferating cell populationwas completely blocked by PD98059 and SB203580,suggesting that mitogen-activated protein kinase activities are essentially required for the process.Conclusion:SAA is a novel inducer for WISH cell apoptosis,and the PTX-insen-sitive pathway is involved in the process. Aim: Serum amyloid A (SAA) is an important mammalian acute reactant. Here, weaim to investigate the effect of SAA on apoptosis and its mechanism of action inhuman amniotic WISH cells. Methods: The expression of formyl peptide receptor (FPRL1), which is reported as a SAA receptor, was tested using RT-PCR and ligated assay with radio-labeled FPRL1 ligand. The effect of SAA on proliferating cell population was evaluated by thymidine incorporation assay. The protein phosphorylation levels and caspase-3 activity were detected by West- ern blot assay. Results: SAA inhibits thymidine incorporation in human amniotic WISH cells. A SAA-induced decrease of proliferating cell population was accom-panied with nuclear condensation and caspase-3 activation in WISH cells, sug-gesting that SAA induces WISH cell apoptosis. Since FPRL1 has been reported as a SAA receptor, we investigated the effects of several FRPL1 agonists on a proliferating cell population in WISH cells. Among the tested FPRL1 agonists, only SAA induced a decrease of proliferating cell population in WISH cells. Onthe downstream signaling of SAA, we found that SAA stimulated extracellular signals-regulated kinase and p38 kinase, which were not inhibited by pertussistoxin (PTX), ruling out the role of PTX-sensitive G-proteins . Furthermore a SAA-induced decrease of proliferating cell population was not affected by PTX, sug-gesting that SAA inhibits WISH cell apoptosis in a PTX-sensitive G-protein-independent manner. A SAA-induced decrease of a proliferating cell population was completely blocked by PD98059 and SB203580, suggesting that mitogen-activated protein kinase activities are essentially required for the process. Confluence: SAA is a novel inducer for WISH cell apoptosis, and the PTX-insen-sitive pathway is involved in the process.